The placebo effect and the autonomic nervous system: evidence for an intimate relationship
Karin
Meissner
0
1
0
Institute of General Practice, Klinikum rechts der Isar, Technische Universita t
,
Orleansplatz 47, 81776 Munich
,
Germany
1
Institute of Medical Psychology, Ludwig-Maximilians-University
,
Goethestrasse 31, 80336 Munich
,
Germany
For many subjectively experienced outcomes, such as pain and depression, rather large placebo effects have been reported. However, there is increasing evidence that placebo interventions also affect end-organ functions regulated by the autonomic nervous system (ANS). After discussing three psychological models for autonomic placebo effects, this article provides an anatomical framework of the autonomic system and then critically reviews the relevant placebo studies in the field, thereby focusing on gastrointestinal, cardiovascular and pulmonary functions. The findings indicate that several autonomic organ functions can indeed be altered by verbal suggestions delivered during placebo and nocebo interventions. In addition, three experimental studies provide evidence for organ-specific effects, in agreement with the current knowledge on the central control of the ANS. It is suggested that the placebo effects on autonomic organ functions are best explained by the model of 'implicit affordance', which assumes that placebo effects are dependent on 'lived experience' rather than on the conscious representation of expected outcomes. Nevertheless, more studies will be needed to further elucidate psychological and neurobiological pathways involved in autonomic placebo effects.
1. INTRODUCTION
The last decade has seen an increased interest in the
occurrence of placebo responses in various conditions.
However, the vast majority of studies examine placebo
effects in subjectively experienced outcomes, such as
pain and depression. Relatively little is known about
the capacity of placebo interventions to alter objectively
assessed endpoints. Based on the meta-analyses of
Hr objartsson & Gtzsche [1 4], a general view has
arisen that placebo interventions do provide
symptomatic relief but do not modify pathophysiologal
processes underlying the disease. However, such a
conclusion may be premature. For example, a subgroup
analysis showed that physical outcome parameters
modulated by the autonomic nervous system (ANS),
such as gastric motility and lung function, improved
in placebo-treated patients when compared with
untreated controls [5]. Furthermore, the latest update
of the meta-analysis of Hr objartsson & Gtzsche [4]
showed a significant pooled placebo effect on lung
function in asthma trials beyond regression-to-the-mean,
although results still carried the risk of bias. Thus,
there is some evidence from systematic reviews that
parameters controlled by the ANS may be amenable
to top-down modulation via placebo interventions.
The ANS provides via elaborated afferent and efferent
fibres a highly specific communication between the organs
and the brain [6]. Therefore, the ANS is a likely
candidate to mediate the effects of placebo interventions on
end-organ functions. As will be shown below, the ANS
also possesses a high functional specificity, which would
even make it possible that organ-specific placebo
effectsaccording to the suggestion givencan occur.
This review will summarize the available evidence for
placebo effects on organ functions that are controlled by
the ANS. First, current psychological approaches to
explain placebo effects are discussed, and a conceptual
framework that can account for placebo effects on
organ functions is provided. Second, the organization
of the ANS, its afferent and efferent pathways and
important relay stations in the brain are summarized.
Third, a comprehensive review of studies examining
placebo effects on autonomic organ functions will be
presented, thereby focusing on the cardiovascular, the
gastrointestinal and the pulmonary system.
2. HOW TO EXPLAIN PLACEBO EFFECTS ON
AUTONOMIC FUNCTIONS Let us imagine a laboratory experiment aimed to investigate whether a placebo intervention can lower 1808
blood pressure, such as recently performed in our
laboratory [7]. The participant, a male, healthy
volunteer, was informed that he would receive one of three
possible interventions: either a homoeopathic remedy
to lower blood pressure or an identically looking
placebo remedy in a double-blinded fashion or no
remedy at all. After filling out some questionnaires,
the experimenter asks him to sit in a comfortable
chair and places a blood pressure cuff around his
arm. The experimenter starts to measure blood
pressure every 5 min and does not tell the participant
about the results. After 30 min, the experimenter
opens the randomization envelope, takes a pill out of
a box and tells the participant that he would now
receive a remedy that would either be a placebo drug
or a homoeopathic drug, which will induce a
measurable fall of blood pressure. The participant swallows
the pill and the experimenter starts to measure blood
pressure every 5 min for (...truncated)